Browsing by Subject "Craniofacial development"

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    Hand1 phosphoregulation within the distal arch neural crest is essential for craniofacial morphogenesis
    (The Company of Biologists, 2014-08) Firulli, Beth A.; Fuchs, Robyn K.; Vincentz, Joshua W.; Clouthier, David E.; Firulli, Anthony B.; Department of Pediatrics, IU School of Medicine
    In this study we examine the consequences of altering Hand1 phosphoregulation in the developing neural crest cells (NCCs) of mice. Whereas Hand1 deletion in NCCs reveals a nonessential role for Hand1 in craniofacial development and embryonic survival, altering Hand1 phosphoregulation, and consequently Hand1 dimerization affinities, in NCCs results in severe mid-facial clefting and neonatal death. Hand1 phosphorylation mutants exhibit a non-cell-autonomous increase in pharyngeal arch cell death accompanied by alterations in Fgf8 and Shh pathway expression. Together, our data indicate that the extreme distal pharyngeal arch expression domain of Hand1 defines a novel bHLH-dependent activity, and that disruption of established Hand1 dimer phosphoregulation within this domain disrupts normal craniofacial patterning.
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    Podoplanin is dispensable for mineralized tissue formation and maintenance in the Swiss outbred mouse background
    (Wiley, 2021) Nakamura, Masako Toda; Zhang, Honghao; Guo, Dayong; Ueharu, Hiroki; Pan, Haichun; Scott, Greg; Harris, Marie; Ray, Manas; Feng, Jiang Q.; Harris, Stephen E.; Bonewald, Lynda F.; Mishina, Yuji; Anatomy, Cell Biology and Physiology, School of Medicine
    Podoplanin, PDPN, is a mucin-type transmembrane glycoprotein widely expressed in many tissues, including lung, kidney, lymph nodes, and mineralized tissues. Its function is critical for lymphatic formation, differentiation of type I alveolar epithelial lung cells, and for bone response to biomechanical loading. It has previously been shown that Pdpn null mice die at birth due to respiratory failure emphasizing the importance of Pdpn in alveolar lung development. During the course of generation of Pdpn mutant mice, we found that most Pdpn null mice in the 129S6 and C57BL6/J mixed genetic background die at the perinatal stage, similar to previously published studies with Pdpn null mice, while all Pdpn null mice bred with Swiss outbred mice survived. Surviving mutant mice in the 129S6 and C57BL6/J mixed genetic background showed alterations in the osteocyte lacunocanalicular network, especially reduced osteocyte canaliculi in the tibial cortex with increased tibial trabecular bone. However, adult Pdpn null mice in the Swiss outbred background showed no overt differences in their osteocyte lacunocnalicular network, bone density, and no overt differences when challenged with exercise. Together, these data suggest that genetic variations present in the Swiss outbred mice compensate for the loss of function of PDPN in lung, kidney, and bone.