Genicular Nerve Anatomy and Its Implication for New Procedural Approaches for Knee Joint Denervation: A Cadaveric Study.

OBJECTIVE: To verify the articular branch contributions in the human knee, delineate their anatomical variance, and outline the limitations of currently applied procedure protocols for denervation of the knee joint. DESIGN: A detailed anatomical dissection. SETTING: Cadavers in residence at the Albert Einstein College of Medicine. SUBJECTS: In total, 24 lower extremity specimens from 14 embalmed cadavers. METHODS: Human cadaveric dissections were performed on 24 lower extremities from 14 embalmed cadavers. RESULTS: This cadaveric study has demonstrated that the anterior knee receives sensory innervations from SMGN, SLGN, LRN, NVI, NVL, RFN, and IMGN. The courses of SMGN, SLGN, RFN, and IMGN are similar to recent anatomical studies. However, discrepancies exist in their relative anatomy to bony and radiographic landmarks. CONCLUSIONS: Genicular denervation using classical anatomical landmarks may not be sufficient to treat the anterior knee joint pain. Our findings illustrate more accurate anatomic landmarks for the three-target paradigm and support additional targets for more complete genicular denervation. This cadaveric study provides robust anatomical findings that can provide a foundation for new anatomical landmarks and targets to improve genicular denervation outcomes.

Anatomic Considerations for a Posterior Endoscopic Approach to the Cricoarytenoid Joint.

OBJECTIVE: This anatomic study considers the feasibility of a posterior endoscopic approach to the cricoarytenoid joint (CAJ) by describing relationships between readily identifiable anatomic landmarks and the posterior CAJ space in cadaver larynges. STUDY DESIGN: Anatomic study. METHODS: Six adult cadaver larynges (2 male, 4 female) were studied. Digital calipers were used for measurements, and Image J software was used for angle calculations. All cricoarytenoid joints were injected with colored gel via a posterior approach using a 27-gauge needle. RESULTS: The average age of the larynges studied was 78.7 ± 10 years. The average posterior CAJ space (pCAJs) length measured 4.95 ± 0.9 mm. The average distance from the superior aspect of the midline cricoid lamina (MCL) to the center of pCAJs and the corniculate cartilage (CC) to the center of the pCAJs were 8.35 ± 1.5 mm and 14.54 ± 1.9 mm, respectively. The average pCAJs angle of declination (AD) from the horizontal plane was 54° ± 6.2°. All 12 cricoarytenoid joints were successfully injected with colored gel via a posterior approach. CONCLUSIONS: The posterior CAJ space can be located surgically using readily identifiable anatomic landmarks. An understanding of this posterior CAJ anatomy may allow for more consistent intra-articular injection and support the development of other CAJ procedures for a range of disorders of vocal fold motion or malposition.

Early and prolonged opportunities to practice suturing increases medical student comfort with suturing during clerkships: Suturing during cadaver dissection.

Medical students are expected to perform common procedures such as suturing on patients during their third-year clerkships. However, these experiences are often viewed by medical students as stressors rather than opportunities for learning. The source of this stress is the lack of instruction on common procedures prior to being asked to observe or perform the procedure on a patient. First-time exposures to procedures in stressful environments may result in decreased confidence in medical students and decrease the frequency with which they perform these procedures in the future. The authors sought to change this paradigm by: (1) introducing a suturing module to first-year medical students in the context of the anatomy dissection laboratory and (2) measuring its effects on student attitudes and behavior over the course of their third-year clerkships when they encounter patients. The authors found that early and prolonged introduction to suturing was associated with increased student confidence relative to suturing a patient. Participation in the suturing module was associated with increased student confidence in identifying suturing instruments (P < 0.001) and suturing patients (P = 0.013). Further it positively affected their behavior as demonstrated by increased performance of suturing events from students exposed to the suturing module. (P < 0.001) This study demonstrates that early and prolonged opportunities to practice a procedural skill in a low-stress environment increases student confidence during patient interactions and alters student behavior.

Unilateral Complete Agenesis of Mesonephric Duct Derivatives in an 82-year-Old Male Cadaver: Embryology, Anatomy and Clinical Considerations.

Development of urogenital anatomy in the human fetus is the result of a complex interplay between multiple different tissues. The time course of development is well documented and the morphologic outcomes of insults at various time points during development are predictable. We present a cadaveric case of unilateral agenesis of the left kidney, ureter, bladder hemitrigone, ureteric opening, seminal vesicle, vas deferens, and epididymis. Failure of development of the mesonephric duct early during embryogenesis, likely between the third and fifth week, caused ipsilateral urogenital organ agenesis.

The Anatomic Relationship of the Tibial Nerve to the Common Peroneal Nerve in the Popliteal Fossa: Implications for Selective Tibial Nerve Block in Total Knee Arthroplasty.

Background. A recently described selective tibial nerve block at the popliteal crease presents a viable alternative to sciatic nerve block for patients undergoing total knee arthroplasty. In this two-part investigation, we describe the effects of a tibial nerve block at the popliteal crease. Methods. In embalmed cadavers, after the ultrasound-guided dye injection the dissection revealed proximal spread of dye within the paraneural sheath. Consequentially, in the clinical study twenty patients scheduled for total knee arthroplasty received the ultrasound-guided selective tibial nerve block at the popliteal crease, which also resulted in proximal spread of local anesthetic. A sensorimotor exam was performed to monitor the effect on the peroneal nerve. Results. In the cadaver study, dye was observed to spread proximal in the paraneural sheath to reach the sciatic nerve. In the clinical observational study, local anesthetic was observed to spread a mean of 4.7 + 1.9 (SD) cm proximal to popliteal crease. A negative correlation was found between the excess spread of local anesthetic and bifurcation distance. Conclusions. There is significant proximal spread of local anesthetic following tibial nerve block at the popliteal crease with possibility of the undesirable motor blocks of the peroneal nerve.

Localization of the Lateral Retinacular Nerve for Diagnostic and Therapeutic Nerve Block for Lateral Knee Pain: A Cadaveric Study.

BACKGROUND: The lateral retinacular nerve (LRN) is a branch of the superior lateral genicular nerve (SLGN) and is believed to contribute to anterolateral knee pain. The precise anatomical pathway of the LRN, however, has not been demonstrated as it relates to the performance of targeted nerve block procedures. OBJECTIVE: To describe the anatomical landmarks for localization of the LRN to facilitate diagnostic and therapeutic nerve blocks in the treatment of chronic anterolateral knee pain. DESIGN: Descriptive study. SETTING: Anatomy dissection laboratory in an academic institution. METHODS: Twenty lower extremities were dissected in 12 cadavers. The sciatic nerve was identified, and its branch to the posterior aspect of the knee, the SLGN, was dissected. The SLGN dissection was continued distally to identify its first branch, the LRN. Two measurements were taken from the branch point on the lateral knee deep to the distal biceps tendon in alignment with the fibular head. A validation study completed in 4 knees was performed as follows: 1 mL of colored dye was injected at the first and second measurements. The cadaveric knee was then dissected to assess the accuracy. MAIN OUTCOME MEASUREMENTS: Localization of the branch point of the LRN from the SLGN via dissection and then direct assessment of injected dye at the measurement points via dissection. RESULTS: The branch point of the LRN from the SLGN was, on average, 5.5 ± 0.66 cm (with a range of 4.5-7.0 cm) proximal to the lateral tibiofemoral joint line in line with the head of the fibula and 2.6 ± 0.62 cm (2.0-4.5 cm) proximal to the tip of the lateral femoral epicondyle. On assessment of the 2 measurements, the measurement 5.5 cm proximal to the lateral joint line accurately targeted the branch point in 100% (4/4) of the knees, whereas the measurement 2.6 cm proximal the tip of the lateral femoral epicondyle accurately targeted the branch point in 75% (3/4) of the knees. CONCLUSION: The results of this study provide 2 dependable landmarks and a description of the path of the LRN, making it possible to accurately target the LRN to diagnose and alleviate lateral knee pain.

Currently Recommended TON Injectate Volumes Concomitantly Block the GON: Clinical Implications for Managing Cervicogenic Headache.

BACKGROUND: Headache (HA) is a significant cause of morbidity globally. Despite many available treatment options, HAs that are refractory to conservative management can be challenging to treat. Third occipital nerve (TON) and greater occipital nerve (GON) irritation are potential etiologic agents of primary and cervicogenic HAs that can be targeted using minimally invasive treatment options such as nerve blocks or radiofrequency ablation. However, a substantial number of patients that undergo radiofrequency ablation do not experience pain relief despite a positive diagnostic medial branch block (MBB). OBJECTIVE: In this study, we investigate the underlying cause for the high rate of false positives associated with MBBs by evaluating injectate spread in cadaveric subjects. STUDY DESIGN: Cadaveric study. SETTING: Academic medical center. METHODS: After obtaining exemption status from our Institutional Review Board, TON injections were performed on 5 preserved cadavers, a total of 10 TONs, using anatomic landmarks, partial dissection, and palpation to guide needle placement. Cadaveric dissections were performed to evaluate the location, vertical spread, and grossly observed injectate coating of the TON and GON for each quantity of methylene blue injectate, 0.3 mL and 0.5 mL, administered. RESULTS: The average distance between the TON and GON at their respective foraminal exit points was 1.81 cm. The average vertical spread for 0.3 mL and 0.5 mL of methylene blue injectate was 2.02 + 0.35 cm and 3.26 + 0.48 cm when performing a TON block. When using 0.3 mL injectate, both the TON and GON were simultaneously coated 60% of the time. After increasing the injectate volume to 0.5 mL, both the TON and GON were simultaneously coated 100% of the time. LIMITATIONS: The cadaveric design of this study presents limitations when translating cadaveric findings to the clinical setting. Also, the small sample size limits its power and generalizability. Lastly, the potential for researcher bias exists as the investigators were not blinded. CONCLUSIONS: This study demonstrates that currently recommended injectate volumes for TON blocks may result in concomitant coating of the GON. Conventional radiofrequency ablation (RFA) of these nerves may not lesion both the TON and GON given its restrictive circumferential lesioning diameter of 5 - 7 mm. As such, interventionalists should consider performing radiofrequency ablation to both the TON and GON after a positive TON block. KEY WORDS: Chronic pain, cervicogenic headache, third occipital nerve, greater occipital nerve, injectate spread, radiofrequency ablation.

Is Genicular Nerve Radiofrequency Ablation Safe? A Literature Review and Anatomical Study.

Genicular nerve radiofrequency ablation (RFA) has recently gained popularity as an intervention for chronic knee pain in patients who have failed other conservative or surgical treatments. Long-term efficacy and adverse events are still largely unknown. Under fluoroscopic guidance, thermal RFA targets the lateral superior, medial superior, and medial inferior genicular nerves, which run in close proximity to the genicular arteries that play a crucial role in supplying the distal femur, knee joint, meniscus, and patella. RFA targets nerves by relying on bony landmarks, but fails to provide visualization of vascular structures. Although vascular injuries after genicular nerve RFA have not been reported, genicular vascular complications are well documented in the surgical literature. This article describes the anatomy, including detailed cadaveric dissections and schematic drawings, of the genicular neurovascular bundle. The present investigation also included a comprehensive literature review of genicular vascular injuries involving those arteries which lie near the targets of genicular nerve RFA. These adverse vascular events are documented in the literature as case reports. Of the 27 cases analyzed, 25.9% (7/27) involved the lateral superior genicular artery, 40.7% (11/27) involved the medial superior genicular artery, and 33.3% (9/27) involved the medial inferior genicular artery. Most often, these vascular injuries result in the formation of pseudoaneurysm, arteriovenous fistula (AVF), hemarthrosis, and/or osteonecrosis of the patella. Although rare, these complications carry significant morbidities. Based on the detailed dissections and review of the literature, our investigation suggests that vascular injury is a possible risk of genicular RFA. Lastly, recommendations are offered to minimize potential iatrogenic complications.

Axillobifemoral bypass: a brief surgical and historical review.

Peripheral artery disease (PAD) occurs when plaque accumulates in the arterial system and obstructs blood flow. Narrowing of the abdominal aorta and the common iliac arteries due to atherosclerotic plaques restricts blood supply to the lower limbs. Clinically, the lower limb symptoms of PAD are intermittent claudication, discoloration of the toes, and skin ulcers, all due to arterial insufficiency. Surgical revascularization is the primary mode of treatment for patients with severe limb ischemia. The objective of the surgical procedure is to bypass a blockage in an occluded major vessel by constructing an alternate route for blood flow using an artificial graft. This article presents information on aortoiliac reconstruction, with an emphasis on axillobifemoral bypass grafting.

Axillobifemoral Bypass Graft: A Student Dissection Experience.

As first-year medical students, we were excited, but nervous, to start the anatomy course. We were prepared to dedicate ourselves to the physical demands of dissection, and the hours of memorizing names and relations of countless anatomic features. We expected to leave the anatomy course with a comprehensive understanding of the human body that we would apply to our future studies and careers. We were not prepared, however, for the experience we had with our cadaver, Lucy.* Lucy was a small woman, but as we learned, she had endured a lot, physically and medically, in her 83 years of life. She had a pacemaker. She had coronary artery disease and a triple bypass procedure. She also had severe peripheral artery disease and had undergone at least one extraordinary surgical graft procedure to maintain blood flow into her lower extremities. The surprise of discovering a small piece of an axillobifemoral bypass graft and then continuing to uncover it, region by region, throughout the anatomy course, brought our dissection experience and our connection to Lucy to a more profound level than we could ever have anticipated. *The name Lucy was chosen as a pseudonym to protect the identity of the cadaver.

Vertebral artery anatomical variations as they relate to cervical transforaminal epidural steroid injections.

OBJECTIVE: To identify and categorize anatomical anomalies of the vertebral artery and determine the relationship of these unexpected variations to the site for cervical transforaminal epidural steroid injections (CTESI). DESIGN: The cervical region and course of the vertebral arteries was dissected in 10 cadavers. Anatomical anomalies of the vertebral arteries were identified and documented. Those that could increase the risk of intra-arterial injection during fluoroscopically guided procedures are detailed. RESULTS: Twenty percent of vertebral arteries were found to have anatomical variations including accessory vessels and lateral loops. These variations placed arterial segments in a portion of the posterior neural foramen where they could be at risk for cannulation during CETSI. In addition, 20% of the vertebral arteries entered the transverse foraminal column at a level other than C6. DISCUSSION: CTESI have become a mainstay in the treatment algorithm for painful cervical radiculopathy. Described techniques take extreme care to avoid cannulation of the vertebral artery during this procedure. Unexpected deviation of the artery, or an arterial segment, into the posterior neural foramen, the target zone for CTESI, increases the risk of intraarterial cannulation during injection. Accordingly, the practitioner must be aware of variant anatomy of the vertebral artery and take all precautions to avoid potential complications that may arise as a consequence.

Safe and successful bone marrow biopsy: an anatomical and CT-based cadaver study.

Bone marrow biopsy is generally a safe procedure. However, infrequently the procedure is associated with serious injuries that are attributed to inadvertent needle penetration of the iliac bone's inner cortex. An evidence-based approach to needle orientation during iliac crest biopsy does not exist. In our study, the posterior to anterior path of the bone marrow needle from the posterior superior iliac spine (PSIS) was studied in human cadavers in two orientations: (1) perpendicularly to the coronal plane (the perpendicular approach) and (2) laterally toward the ipsilateral anterior superior iliac spine (ASIS) (the lateral approach). The biopsy needle was deliberately advanced through the inner ilial cortex in both approaches. Dissections and imaging studies were done to identify the relationship of the penetrating needle to internal structures. Both approaches begin with a perpendicular puncture of the outer cortex at the PSIS. The perpendicular approach proceeds anteriorly whereas in the lateral approach the needle is reoriented toward the ipsilateral ASIS before advancing. The lateral approach caused less damage to neurovascular structures and avoided the sacroiliac joint compared to the perpendicular approach. This procedure is best done in the lateral decubitus position. Proper use of the lateral approach should obviate many of the complications reported in the literature.

Intraforaminal location of thoracolumbar anterior medullary arteries.

BACKGROUND: Transforaminal epidural steroid injection (TFESI) is a widely utilized interventional pain technique for radicular pain. Although the six o'clock position of the pedicle in the so-called "safe triangle" has been used as a target location, there have been a number of reported catastrophic complications of this procedure, including paraplegia. The mechanism of this has been attributed to the intravascular injection of steroids. The goal of this study was to examine the intraforaminal location of thoracolumbar medullary arteries which would help guide pain physicians in developing safer techniques and guidelines. METHODS: Twenty-four (24) embalmed cadavers were dissected and examined for the presence and distribution of thoracolumbar anterior medullary arteries. Access to the anterior surface of the spinal cord was made via anterior corpectomy from C2 to S5. Each medullary artery's course was determined by dissection from its origin, the anterior spinal artery, through the intervertebral foramen. The foramen was subsequently opened in the coronal plane, and the intraforaminal location of the artery, its diameter, and its relation to other foraminal structures were examined and measured. RESULTS: In the thoracolumbar foramina (T4-L2), 39 anterior medullary arteries were found, including 23 great medullary arteries (Adamkiewicz artery). One Adamkiewicz artery was found to be located in the left S2 foramen and was not included in the statistical analysis. Of the analyzed 39 anterior medullary arteries, 29 (74%) were located in the upper 1/3 of the foramen, 9 (23%) were located in the middle, and 1 (3%) artery was located in the lower 1/3. In relation to the dorsal root ganglion--ventral root complex, 21 (54%) arteries were located anterosuperiorly, 16 (41%) anteriorly, and 2 (5%) anteroinferiorly. The average intraforaminal artery diameter was 1.20 mm (0.84-1.91 mm). At thoracolumbar levels, the artery is almost always (92% ± 15%) located anterosuperior to the nerve. At typical thoracic levels, it is less often anterosuperior (38% ± 19%), but more often anterior to the nerve. CONCLUSIONS: At thoracolumbar levels, if needles were to encounter an artery, they are most likely to do so if placed anterosuperior to the nerve. Encountering an artery anterosuperior to the nerve is less likely at typical thoracic levels, but the likelihood is far from negligible. Pain physicians should be cognizant of this when considering optimal needle placement during transforaminal epidural steroid injections.

Interprofessional student education: exchange program between Albert Einstein College of Medicine and Pacific College of Oriental Medicine.

The growing popularity of complementary and alternative medicine (CAM), of which estimated 38% of adults in the United States used in 2007, has engendered changes in medical school curricula to increase students' awareness of it. Exchange programs between conventional medical schools and CAM institutions are recognized as an effective method of interprofessional education. The exchange program between Albert Einstein College of Medicine (Einstein, Yeshiva University) and Pacific College of Oriental Medicine, New York campus (PCOM-NY) is in its fifth year and is part of a broader relationship between the schools encompassing research, clinical training, interinstitutional faculty and board appointments, and several educational activities. The Einstein/PCOM-NY student education exchange program is part of the Einstein Introduction to Clinical Medicine Program and involves students from Einstein learning about Chinese medicine through a lecture, the experience of having acupuncture, and a four-hour preceptorship at the PCOM outpatient clinic. The students from PCOM learn about allopathic medicine training through an orientation lecture, a two-and-a-half-hour dissection laboratory session along side Einstein student hosts, and a tour of the clinical skills center at the Einstein campus. In the 2011/2012 offering of the exchange program, the participating Einstein and PCOM students were surveyed to assess the educational outcomes. The data indicate that the exchange program was highly valued by all students and provided a unique learning experience. Survey responses from the Einstein students indicated the need for greater emphasis on referral information, which has been highlighted in the literature as an important medical curriculum integrative medicine competency.

Proximal iliotibial band syndrome: what is it and where is it?

OBJECTIVE: To describe the clinical and MR imaging features of a unique strain at the iliac tubercle enthesis. While this strain appeared to correspond to the iliotibial band (IT band) enthesis, the literature regarding the IT band origin was discrepant. As such, our second goal was to prove that the IT band originated at the iliac tubercle, through cadaveric dissection. MATERIALS AND METHODS: Three musculoskeletal radiologists prospectively reviewed 67 consecutive bony pelvis MRI studies from October 2006 through September 2008 using either 3, 1.5, or 0.3 T units. Seven cases demonstrating strain at the iliac tubercle enthesis were identified and reviewed by consensus. History and patient demographics were reviewed. Cadaveric dissection was performed to delineate the anatomy of the proximal IT band. RESULTS: Seven out of 67 individuals, all women, were identified with strain at the level of the iliac tubercle (prevalence 10%). Four of seven were athletes, three were overweight. Patients presented with pain and tenderness at the iliac tubercle. Anatomic dissection confirmed that iliotibial band originates along the margin of the iliac crest with dominant fibers condensing on the iliac tubercle. CONCLUSION: Proximal IT band strain represents a unique injury that should be considered in patients who are female athletes or older overweight women who present with pain and tenderness at the iliac tubercle. Imaging of this entity must include the iliac tubercle, which is often excluded in standard hip MRI.

Nerve injury during uterosacral ligament fixation: a cadaver study.

INTRODUCTION AND HYPOTHESIS: The objective of this study was to identify nerve(s) vulnerable to entrapment during uterosacral ligament fixation (USLF), which could cause postoperative lower extremity pain previously described in the literature. METHODS: Preserved cadavers in a medical anatomy course were used. Before the students' pelvic dissections, a 2-0 prolene suture was placed in the middle third of each left uterosacral ligament visualized. The sutures were re-evaluated at the end of the course. RESULTS: Nine sutures remained in place after the course, and one entrapped a nerve. It was part of the inferior hypogastric plexus, included fibers from S2 and S3, and radiated to the bladder and rectum. The posterior femoral cutaneous nerve was lateral and posterior to this nerve. CONCLUSIONS: The inferior hypogastric plexus is vulnerable during USLF. Entrapment of S2 and S3 fibers could cause pain in their respective dermatomes and could be responsible for the postoperative pain previously described.

Innervation of the levator ani muscles: description of the nerve branches to the pubococcygeus, iliococcygeus, and puborectalis muscles.

We described the innervation of the levator ani muscles (LAM) in human female cadavers. Detailed pelvic dissections of the pubococcygeus (PCM), iliococcygeus (ICM), and puborectalis muscles (PRM) were performed on 17 formaldehyde-fixed cadavers. The pudendal nerve and the sacral nerves entering the pelvis were traced thoroughly, and nerve branches innervating the LAM were documented. Histological analysis of nerve branches entering the LAM confirmed myelinated nerve tissue. LAM were innervated by the pudendal nerve branches, perineal nerve, and inferior rectal nerve (IRN) in 15 (88.2%) and 6 (35.3%) cadavers, respectively, and by the direct sacral nerves S3 and/or S4 in 12 cadavers (70.6%). A variant IRN, independent of the pudendal nerve, was found to innervate the LAM in seven (41.2%) cadavers. The PCM and the PRM were both primarily innervated by the pudendal nerve branches in 13 cadavers (76.5%) each. The ICM was primarily innervated by the direct sacral nerves S3 and/or S4 in 11 cadavers (64.7%).

Anatomic variations of the pelvic floor nerves adjacent to the sacrospinous ligament: a female cadaver study.

Our objective was to document variations in the topography of pelvic floor nerves (PFN) and describe a nerve-free zone adjacent to the sacrospinous ligament (SSL). Pelvic floor dissections were performed on 15 female cadavers. The course of the PFN was described in relation to the ischial spine (IS) and the SSL. The pudendal nerve (PN) passed medial to the IS and posterior to the SSL at a mean distance of 0.6 cm (SD = +/-0.4) in 80% of cadavers. In 40% of cadavers, an inferior rectal nerve (IRN) variant pierced the SSL at a distance of 1.9 cm (SD = +/-0.7) medial to the IS. The levator ani nerve (LAN), coursed over the superior surface of the SSL-coccygeus muscle complex at a mean distance of 2.5 cm (SD = +/-0.7) medial to the IS. Anatomic variations were found which challenge the classic description of PFN. A nerve-free zone is situated in the medial third of the SSL.

Ectodermal FGFs induce perinodular inhibition of limb chondrogenesis in vitro and in vivo via FGF receptor 2.

The formation of cartilage elements in the developing vertebrate limb, where they serve as primordia for the appendicular skeleton, is preceded by the appearance of discrete cellular condensations. Control of the size and spacing of these condensations is a key aspect of skeletal pattern formation. Limb bud cell cultures grown in the absence of ectoderm formed continuous sheet-like masses of cartilage. With the inclusion of ectoderm, these cultures produced one or more cartilage nodules surrounded by zones of noncartilaginous mesenchyme. Ectodermal fibroblast growth factors (FGF2 and FGF8), but not a mesodermal FGF (FGF7), substituted for ectoderm in inhibiting chondrogenic gene expression, with some combinations of the two ectodermal factors leading to well-spaced cartilage nodules of relatively uniform size. Treatment of cultures with SU5402, an inhibitor FGF receptor tyrosine kinase activity, rendered FGFs ineffective in inducing perinodular inhibition. Inhibition of production of FGF receptor 2 (FGFR2) by transfection of wing and leg cell cultures with antisense oligodeoxynucleotides blocked appearance of ectoderm- or FGF-induced zones of perinodular inhibition of chondrogenesis and, when introduced into the limb buds of developing embryos, led to shorter, thicker, and fused cartilage elements. Because FGFR2 is expressed mainly at sites of precartilage condensation during limb development in vivo and in vitro, these results suggest that activation of FGFR2 by FGFs during development elicits a lateral inhibitor of chondrogenesis that limits the expansion of developing skeletal elements.