ABSTRACT
We studied the expression of several homeobox genes of the HOX family in the adult human intestinal mucosa. HOX genes are regulatory genes homologous to the homeotic genes controlling the body plan of the fruit fly Drosophila melanogaster. The HOX genes are distributed in four homologous HOX loci termed HOX-A, B, C and D, located on four different chromosomes. They have been found to be expressed in many embryonic tissues and axial structures like the central nervous system, the spine and in selected adult cells. The expression of 39 HOX genes belonging to HOX-A, B, C and D was studied by in situ hybridization on specimens of mucosa from normal adult colon. All the genes studied were shown to be expressed in these tissues, but the genes belonging to the four loci showed different localization within the colonic mucosa: HOX-A genes are expressed in undifferentiated proliferating cells at the base of the crypts, HOX-C genes in differentiated cells at the apex of the crypts and HOX-B and HOX-D genes are weakly expressed along the entire crypt length. Expression of some of these genes was also studied in differentiating CaCo-2 cells and tumoral tissues. In particular, in colonic adenocarcinomatous cells, some HOX-A genes appear to be abundantly expressed confirming the presence of these gene products in normal.
Subject(s)
Colon/metabolism , Homeodomain Proteins/genetics , Intestinal Mucosa/metabolism , Multigene Family/genetics , Adenocarcinoma/genetics , Adenocarcinoma/pathology , Adult , Caco-2 Cells , Colonic Neoplasms/genetics , Colonic Neoplasms/pathology , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Gene Expression , Humans , In Situ Hybridization , RNA, Messenger/genetics , RNA, Messenger/metabolismABSTRACT
We report three families with dominant unilateral renal adysplasia without vesico-ureteral reflux. No dysmorphia or anomalies were evident in the reproductive system. Ophthalmological examination excluded the presence of optic nerve coloboma or other ocular anomalies. No mutations were detected in the EMX(2) and in PAX(2) genes of affected members. Other homeobox genes could be responsible for this anomaly in these three families.
Subject(s)
Genetic Heterogeneity , Kidney Diseases/genetics , Urogenital Abnormalities/genetics , Adult , DNA-Binding Proteins/genetics , Female , Homeodomain Proteins/genetics , Humans , Infant , Infant, Newborn , Kidney Diseases/etiology , Kidney Diseases/pathology , Male , PAX2 Transcription Factor , Pedigree , Transcription Factors/genetics , Urogenital Abnormalities/etiologyABSTRACT
The molecular mechanisms that activate morphogenesis of cerebral cortex are currently the subject of intensive experimental analysis. Transcription factor genes of the homeobox, basic helix-loop-helix (bHLH) and zinc-finger families have recently been shown to have essential roles in this process. However, the actual selector genes activating corticogenesis have not yet been identified. Here we show that high-level expression of at least one functional allele of either of the homeobox genes Emx2 or Pax6 in the dorsal telencephalon is necessary and sufficient to stably activate morphogenesis of cerebral cortex and to repress that of adjacent structures, such as striatum.
Subject(s)
Basal Ganglia/abnormalities , Cerebral Cortex/abnormalities , Homeodomain Proteins/metabolism , Nervous System Malformations/embryology , Alleles , Animals , Antigens, Differentiation/biosynthesis , Antigens, Differentiation/genetics , Basal Ganglia/metabolism , Basal Ganglia/pathology , Cell Differentiation , Cerebral Cortex/metabolism , Cerebral Cortex/pathology , Down-Regulation , Eye Proteins , Gene Expression Regulation, Developmental , Homeodomain Proteins/genetics , Immunohistochemistry , In Situ Hybridization , Mice , Mice, Knockout , Mice, Mutant Strains , Morphogenesis , Nervous System Malformations/metabolism , Nervous System Malformations/pathology , PAX6 Transcription Factor , Paired Box Transcription Factors , RNA, Messenger/analysis , RNA, Messenger/biosynthesis , Repressor Proteins , Stem Cells/cytology , Transcription FactorsABSTRACT
It has recently been demonstrated that the transcription factor genes Emx2 and Pax6, expressed in the developing cerebral cortex along two complementary tangential gradients, are essential for the shaping of the cortical areal profile at late developmental ages, when cortical neuronogenesis is almost completed. In this study we addressed the question of whether cortical regionalization is already affected in Emx2 and Pax6 loss of function mutants at the beginning of neuronogenesis. By comparing expression patterns of selected molecular markers in these mutants at this age, we found that: (i) Emx2 and Pax6 are necessary for the establishment of their own specific expression profiles and are able to down-regulate each other; and (ii) absence of functional EMX2 or PAX6 proteins results in reduction of caudal-medial and rostral-lateral cortical regions, respectively, as well as in impairment of the WNT signalling center at the medial-caudal edge of the cortical field, crucial for cortical growth. These results suggest that pre-neuronogenic cortical regionalization may rely on mutual interactions between these two transcription factors and that the late areal phenotype of Emx2(-/-) and Pax6(-/-) mutants may possibly arise from both misconfiguration of the cortical molecular protomap and distortion of the cortical growth profile.
