A study of the role of Msx genes in mammalian orgenogenesis

为了激发MSH类同源物基因Msx 1和Msx 2在哺乳动物有机体中的作用，我们已经分析了这些基因的knockout老鼠，我们认为在有机体发生期间会发生在外延-中间体相互作用中。我们先前已经展示了Msx1 induced in the dental mesenchyme by BMP 4 and FGF 4 which are secreted from dental epithelium， in turn， induces BMP 4， LEF1， and syndecan1 in the dental mesenchyme and that Msx1 functions as a signal mediator between dental epithelium and mesenchyme。Msx 2突变体显示了搪瓷形成的失败。在第一个搪瓷结的突变体中，减少的凋亡似乎是这种发展不正常性的一个原因。《信号之路》， I。e.，BMP 4 ￣ Msx2 ￣ BMP 4 ￣ apoptosis exists and is considered to be essential for normal Management of enamel organ。Msx 2突变体也被描述为异常骨骼和卡通形成。这块木板和一块木板的数量已经消失了，生长板和骨的厚度已经消失了。 ... More 他在变种人身上。对于osteoblasts Cbfa1， osteonectin， Alp， osteopontin， BSP， and osteocalsin were decreased in the developing long bone of the mutants。ColII、ColX、PTHrP和PTH/PTHrP受体的分化标记的表达也被减少到突变体中。MSx 2可能会对这些基因的转录规则扮演一个重要的角色。Msx1 · Msx2 double mutants manifested hypoplastic thumbs， polydactyly， syndactyly， and absence of radius and tibia。在E10.5双突变体肢体泡沫，在极化活动区（ZPA）的Shh表达不能通过原位杂交Anf Fgf 4表达将从皮触顶脊的后半部（AER）转移到外半部。Msx 1和Msx 2功能上游，需要在ZPA的肢体中表达Shh。Bmp 4表达在进展区的外部部分中也可能无法在双突变体中检测到。这些基因的不正常表达是一个想法，因为它们是由于hypoplastic thumbs、polydactyly，以及放射性和tibia的缺失。Furthermore，Bmp 4表达被市场上减少并抑制了凋亡症在E10.5双突变体的数字化区域可见。在数字化区域抑制凋亡可能是多方面造成的。Msx 1和Msx 2需要Bmp 4表达在进展区和数字间区域的外部部分，以及信号路径， i。e. e. ., BMP and FGF from AER ￣ Msx1 and Msx2 ￣ BMP 4 in progress zone and interdigital region functions for normal limb formation。在摘要中，Msx 1和Msx 2认为有机体过程中作为重要的信号介质发挥作用。Less（低）

To elucidate the role of the msh-class homebox genes Msx1 and Msx2 in mammalian organogenesis, we have analyzed knockout mice of these genes which are thought to be involved in epithelial-mesenchymal interaction during organogenesis. We had previously shown that Msx1 induced in the dental mesenchyme by BMP4 and FGF4 which are secreted from dental epithelium, in turn, induces BMP4, LEF1, and syndecan 1 in the dental mesenchyme and that Msx1 functions as a signal mediator between dental epithelium and mesenchyme. Msx2 mutants showed a failure of enamel formation. The reduced apoptosis in the first enamel knot of mutants seemed to be a cause of this developmental abnormality. The signaling pathway, i. e., BMP4→Msx2→BMP4→apoptosis exists and is considered to be essential for normal development of enamel organ. Msx2 mutants also manifested abnormal bone and cartliage formation. The number of osteoblasts and osteoclasts was deminished and the thickness of growth plate and cortical bone was t … More hin in the mutants. Expression of the differentiation markers for osteoblasts Cbfa1, osteonectin, Alp, osteopontin, BSP, and osteocalsin were decreased in the developing long bone of the mutants. Expression of the differentiation markers for chondrocytes ColII, ColX, PTHrP, and PTH/PTHrP receptor were also reduced in the mutants. Msx2 may play an important role for the transcriptional regulation of these genes. Msx1 ・ Msx2 double mutants manifested hypoplastic thumbs, polydactyly, syndactyly, and absence of radius and tibia. In E10.5 double mutants limb bud, the expression of Shh in the zone of polarizing activity (ZPA) could not be detecedby in situ hybridization anf Fgf4 expression was shifted from the posterior half of the apical ectdermal ridge (AER) to the anterior half. Msx1 and Msx2 function upstream of Shh, and are required for the expression of Shh in the limb ZPA. Bmp4 expression in the anterior portion of the progress zone also could not be detected in double mutants. The abnormal expression of these genes is thought to cause hypoplastic thumbs, polydactyly, and absence of radius and tibia. Furthermore, Bmp4 expression was markedly reduced and inhibition of apoptosis was observed in E10.5 interdigital region of double mutants. Inhibition of apoptosis in interdigital region can cause polydactyly. Msx1 and Msx2 are required for the Bmp4 expression in the anterior portion of progress zone and interdigital region, and the signal pathway, i. e. ., BMP and FGF from AER→Msx1 and Msx2→BMP4 in progress zone and interdigital region functions for normal limb formation. In summary, Msx1 and Msx2 are thought to function as important signal mediators in the epithelial-mesenchymal interaction during organogenesis. Less