Comparative Radiographic Analysis of the Width of the Lesser Digit Proximal Phalangeal Heads.

BACKGROUND: Digital deformities represent a common presenting abnormality and target for surgical intervention in podiatric medicine and surgery. The objective of this investigation was to compare the radiographic width of the heads of the lesser digit proximal phalanges. METHODS: One hundred fifty consecutive feet with a diagnosis of digital deformity and performance of weightbearing radiographs were analyzed. The maximum width of the heads of the lesser digit proximal phalanges were recorded from the radiographs using computerized digital software. RESULTS: The mean ± standard deviation of the head of the second digit proximal phalanx was 9.74 ± 0.87 mm (range, 7.94-11.78 mm); the head of the third digit proximal phalanx, 9.00 ± 0.91 mm (range,7.27-10.94 mm); the head of the fourth digit proximal phalanx, 8.49 ± 1.01 mm (range, 5.57-10.73 mm); and the head of the fifth digit proximal phalanx, 8.67 ± 0.89 mm (range, 6.50-11.75 mm). The width of the head of the proximal phalanx decreased from the second digit to the third digit (P < .001), decreased from the third digit to the fourth digit (P < .001), and then increased from the fourth digit to the fifth digit (P = .032). CONCLUSIONS: The results of this investigation provide evidence in support of an anatomical and structural contribution to digital deformities. The width of the heads of the lesser digit proximal phalanges decreased from the second to the third to the fourth toes, and then subsequently increased with the fifth proximal phalangeal head.

HOM-C genes, Wnt signaling and axial patterning in the C. elegans posterior ventral epidermis.

Wnt signaling and HOM-C/Hox genes pattern cell fate along the anterior/posterior axis in many animals. In general, Wnt signaling participates in establishing the anterior/posterior axis, whereas HOM-C genes confer regional identities to cells along the axis. However, recent work in non-bilaterial metazoans suggests that the ancestral patterning system relied on Wnts, with a later co-option of HOM-C genes to replace Wnts in regional patterning. Here we provide direct experimental support for this model from C. elegans, where a regional Wnt patterning system is uncovered in HOM-C gene mutants. Anterior/posterior patterning of P11/P12 cell fate in the C. elegans tail is normally dependent on the HOM-C gene egl-5/Abdominal-B. If the HOM-C gene mab-5/fushi tarazu is also mutant, however, a Wnt signal can promote P12 fate in the absence of egl-5. Furthermore, transcription of egl-5 in the P12.pa cell is influenced by an autoregulatory element that is essential in wild type, but not in mab-5 egl-5 double mutants, identifying regulatory parallels between P12 cell fate specification and egl-5 transcriptional regulation in the P12 lineage. Together, our results identify complex regulatory relationships among signaling pathways and HOM-C genes, and uncover a layering of patterning systems that may reflect their evolutionary history.

Genetic redundancy in endoderm specification within the genus Caenorhabditis.

Specification of the endoderm precursor, the E cell, in Caenorhabditis elegans requires a genomic region called the Endoderm Determining Region (EDR). We showed previously that end-1, a gene within the EDR encoding a GATA-type transcription factor, restores endoderm specification to embryos deleted for the EDR and obtained evidence for genetic redundancy in this process. Here, we report molecular identification of end-3, a nearby paralog of end-1 in the EDR, and show that end-1 and end-3 together define the endoderm-specifying properties of the EDR. Both genes are expressed in the early E lineage and each is individually sufficient to specify endodermal fate in the E cell and in non-endodermal precursors when ectopically expressed. The loss of function of both end genes, but not either one alone, eliminates endoderm in nearly all embryos and results in conversion of E into a C-like mesectodermal precursor, similar to deletions of the EDR. While two putative end-1 null mutants display no overt phenotype, a missense mutation that alters a residue in the zinc finger domain of END-3 results in misspecification of E in approximately 9% of mutant embryos. We report that the EDR in C. briggsae, which is estimated to have diverged from C. elegans approximately 50--120 myr ago, contains three end-like genes, resulting from both the ancient duplication that produced end-1 and end-3 in C. elegans, and a more recent duplication of end-3 in the lineage specific to C. briggsae. Transgenes containing the C. briggsae end homologs show E lineage-specific expression and function in C. elegans, demonstrating their functional conservation. Moreover, RNAi experiments indicate that the C. briggsae end genes also function redundantly to specify endoderm. We propose that duplicated end genes have been maintained over long periods of evolution, owing in part to their synergistic function.

lin-17/Frizzled and lin-18 regulate POP-1/TCF-1 localization and cell type specification during C. elegans vulval development.

The Caenorhabditis elegans vulva is comprised of highly similar anterior and posterior halves that are arranged in a mirror symmetric pattern. The cell lineages that form each half of the vulva are identical, except that they occur in opposite orientations with respect to the anterior/posterior axis. We show that most vulval cell divisions produce sister cells that have asymmetric levels of POP-1 and that the asymmetry has opposite orientations in the two halves of the vulva. We demonstrate that lin-17 (Frizzled type Wnt receptor) and lin-18 (Ryk) regulate the pattern of POP-1 localization and cell type specification in the posterior half of the vulva. In the absence of lin-17 and lin-18, posterior lineages are reversed and resemble anterior lineages. These experiments suggest that Wnt signaling pathways reorient cell lineages in the posterior half of the vulva from a default orientation displayed in the anterior half of the vulva.

C. elegans LIN-18 is a Ryk ortholog and functions in parallel to LIN-17/Frizzled in Wnt signaling.

Wnt proteins are intercellular signals that regulate various aspects of animal development. In Caenorhabditis elegans, mutations in lin-17, a Frizzled-class Wnt receptor, and in lin-18 affect cell fate patterning in the P7.p vulval lineage. We found that lin-18 encodes a member of the Ryk/Derailed family of tyrosine kinase-related receptors, recently found to function as Wnt receptors. Members of this family have nonactive kinase domains. The LIN-18 kinase domain is dispensable for LIN-18 function, while the Wnt binding WIF domain is required. We also found that Wnt proteins LIN-44, MOM-2, and CWN-2 redundantly regulate P7.p patterning. Genetic interactions indicate that LIN-17 and LIN-18 function independently of each other in parallel pathways, and different ligands display different receptor specificities. Thus, two independent Wnt signaling pathways, one employing a Ryk receptor and the other a Frizzled receptor, function in parallel to regulate cell fate patterning in the C. elegans vulva.

The T-box transcription factors TBX-37 and TBX-38 link GLP-1/Notch signaling to mesoderm induction in C. elegans embryos.

The four-cell C. elegans embryo contains two sister cells called ABa and ABp that initially have equivalent abilities to produce ectodermal cell types. Multiple Notch-mediated interactions occur during the early cell divisions that diversify the ABa and ABp descendants. The first interaction determines the pattern of ectodermal cell types produced by ABp. The second interaction induces two ABa granddaughters to become mesodermal precursors. We show that T-box transcription factors called TBX-37 and TBX-38 are essential for mesodermal induction, and that these factors are expressed in ABa, but not ABp, descendants. We provide evidence that the first Notch interaction functions largely, if not entirely, to prevent TBX-37, TBX-38 expression in ABp descendants. Neither the second Notch interaction nor TBX-37, TBX-38 alone are sufficient for mesodermal induction, indicating that both must function together. We conclude that TBX-37, TBX-38 play a key role in distinguishing the outcomes of two sequential Notch-mediated interactions.