The stem cells that maintain and repair the postnatal skeleton remain undefined. One model suggests that perisinusoidal mesenchymal stem cells (MSCs) give rise to osteoblasts, chondrocytes, marrow stromal cells, and adipocytes, although the existence of these cells has not been proven through fate-mapping experiments. We demonstrate here that expression of the bone morphogenetic protein (BMP) antagonist gremlin 1 defines a population of osteochondroreticular (OCR) stem cells in the bone marrow. OCR stem cells self-renew and generate osteoblasts, chondrocytes, and reticular marrow stromal cells, but not adipocytes. OCR stem cells are concentrated within the metaphysis of long bones not in the perisinusoidal space and are needed for bone development, bone remodeling, and fracture repair. Grem1 expression also identifies intestinal reticular stem cells (iRSCs) that are cells of origin for the periepithelial intestinal mesenchymal sheath. Grem1 expression identifies distinct connective tissue stem cells in both the bone (OCR stem cells) and the intestine (iRSCs).

In the adult intestine, an organized array of finger-like projections, called villi, provide an enormous epithelial surface area for absorptive function. Villi first emerge at embryonic day (E) 14.5 from a previously flat luminal surface. Here, we analyze the cell biology of villus formation and examine the role of paracrine epithelial Hedgehog (Hh) signals in this process. We find that, before villus emergence, tight clusters of Hh-responsive mesenchymal cells form just beneath the epithelium. Cluster formation is dynamic; clusters first form dorsally and anteriorly and spread circumferentially and posteriorly. Statistical analysis of cluster distribution reveals a patterned array; with time, new clusters form in spaces between existing clusters, promoting approximately four rounds of villus emergence by E18.5. Cells within mesenchymal clusters express Patched1 and Gli1, as well as Pdgfrα, a receptor previously shown to participate in villus development. BrdU-labeling experiments show that clusters form by migration and aggregation of Hh-responsive cells. Inhibition of Hh signaling prevents cluster formation and villus development, but does not prevent emergence of villi in areas where clusters have already formed. Conversely, increasing Hh signaling increases the size of villus clusters and results in exceptionally wide villi. We conclude that Hh signals dictate the initial aspects of the formation of each villus by controlling mesenchymal cluster aggregation and regulating cluster size.epithelial-mesenchymal cross-talk | field pattern | villus morphogenesis

Background & Aims Infantile hypertrophic pyloric stenosis (IHPS) is a common birth anomaly characterized by obstruction of the pyloric lumen. A genome-wide association study implicated NKX2-5, which encodes a transcription factor that is expressed in embryonic heart and pylorus, in the pathogenesis of IHPS. However, the function of the NKX2-5 in pyloric smooth muscle development has not been directly examined. We investigated the pattern of Nkx2-5 during the course of murine pyloric sphincter development and examined co-expression of Nkx2-5 with Gata3 and Sox9—other transcription factors with pyloric-specific mesenchymal expression. We also assessed pyloric sphincter development in mice with disruption of Nkx2-5 or Gata3. Methods We used immunofluorescence analysis to compare levels of NKX2-5, GATA3, and SOX9 in different regions of smooth muscle cells. Pyloric development was assessed in mice with conditional or germline deletion of Nkx2-5 or Gata3, respectively. Results Gata3, Nkx2-5, and Sox9 were co-expressed in differentiating smooth muscle cells of a distinct fascicle of the pyloric outer longitudinal muscle (OLM). Expansion of this fascicle coincided with development of the pyloric sphincter. Disruption of Nkx2-5 or Gata3 caused severe hypoplasia of this fascicle and alters pyloric muscle shape. Although expression of Sox9 required Nkx2-5 and Gata3, there was no apparent hierarchical relationship between Nkx2-5 and Gata3 during pyloric OLM development. Conclusions Nkx2-5 and Gata3 are independently required for the development of a pyloric OLM fascicle, which required for pyloric sphincter morphogenesis, in mice. These data indicate that regulatory changes that alter Nkx2-5 or Gata3 expression could contribute to pathogenesis of IHPS.

SUMMARY:The study was conducted on the prostate gland of Gaddi goat from one day old to more than five years of age divided into three groups viz; Prepubertal (1 day old to < 18 months of age), Pubertal (18 months to < 5 yrs of age) and Postpubertal (> 5 yrs of age). The prostate comprised of corpus prostatae, a band like structure close to the junction of vesicular gland with the urethra, and the pars disseminate which extended in urethra well from its origin to the point of duct of bulbourethral gland. Microscopically, the corpus prostatae comprised of two compact glandular masses lying one over the other, dorsally over the origin of pelvic urethra covered by a thick fibro-reticular capsule. The gland composed of end pieces (luminated and non-luminated acini) and ducts arranged in lobulated fashion. The thickness of inter and intralobular connective tissue decreased with increased age at the expense of the growth of paraenchyma. With age the luminated secretory end pieces increased, while the non-luminatedend pieces decreased in the lobules of the gland. Glandular parenchyma were rich in mucous components by 6 month age serous and mucous components became almost equal and at 12 month age majority of the secretory end pieces turned in to serous type. The excretory ducts which were lined by stratified cuboidal epithelium in one day old kids changed to transitional epithelium in late prepubertal and pubertal animals. The glandular elements were PAS and Best's carmine reactive while interstitial connective tissue was non reactive. Mild alkaline phosphatase reaction was evident in the interstitial connective tissue cells. A strong acid phosphatase reaction was evident in the endothelium. BPB reaction for protein was moderate to intense. Ducts and acini were PAS and Alcian Blue reactive. The reaction for glycogen and AMPS contents in the gland increased with age. It was very intense in the pubertal animals. Moderate DNA activity, mild to moderate alkaline and acid phosphatases in the glandular acini and ductal epithelium revealed functionally active secretory glands particularly in the pubertal animals.

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