Altered sacral neural crest development in Pax3 spina bifida mutants underlies deficits of bladder innervation and function.
Altered sacral neural crest development in Pax3 spina bifida mutants underlies deficits of bladder innervation and function.
复制标题
PAX3脊柱裂裂突变体中的s骨神经rest发育改变了膀胱神经和功能的缺陷。
DOI：
10.1016/j.ydbio.2021.03.024
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发表时间：
2021-08
影响因子：
2.7
通讯作者：
Southard-Smith EM
中科院分区：
文献类型：
--
作者：
Deal KK;Chandrashekar AS;Beaman MM;Branch MC;Buehler DP;Conway SJ;Southard-Smith EM
脊柱裂（SB）的小鼠模型已被用于识别影响神经形成和神经管闭合的基因、发育过程和环境因素。除了突出的神经管缺陷，神经系统的其他方面也会受到影响，在SB中，基本身体功能（如排尿）会发生显著变化。SB患者经常发生膀胱功能障碍，SB胎儿表现出膀胱神经和平滑肌密度降低，尽管这些缺陷的发育起源尚未确定。Pax 3斑点延迟（Pax 3Sp-d）SB小鼠模型是存活至妊娠晚期的极少数小鼠SB模型之一。通过分析Pax 3Sp-d突变体，我们试图通过追踪骶神经嵴（NC）发育、盆神经节神经元分化和评估膀胱神经纤维密度来确定SB中膀胱神经支配的改变。在Pax 3Sp-d/Sp-d胎鼠中，我们观察到Sox 10 + NC衍生祖细胞（NCPs）迁移延迟，盆神经节神经发生不足，膀胱壁神经支配密度降低。我们进一步将NC特异性Pax 3缺失与组成型Pax 3Sp-d等位基因相结合，以产生可行的Pax 3突变体来检查膀胱神经支配和出生后膀胱功能的后期阶段。神经嵴特异性缺失Pax 3 flox等位基因，使用Sox 10-cre驱动程序，与组成性Pax 3Sp-d突变相结合，产生了出生后有活力的后代，这些后代表现出膀胱功能的改变以及膀胱壁神经支配的减少和膀胱颈处副神经节之间的连接性的改变。结合，结果表明，Pax 3在骶骨NC中起着关键作用，对于盆神经节内自主神经元的神经发生和分化的启动至关重要。
Mouse models of Spina bifida (SB) have been instrumental for identifying genes, developmental processes, and environmental factors that influence neurulation and neural tube closure. Beyond the prominent neural tube defects, other aspects of the nervous system can be affected in SB with significant changes in essential bodily functions such as urination. SB patients frequently experience bladder dysfunction and SB fetuses exhibit reduced density of bladder nerves and smooth muscle although the developmental origins of these deficits have not been determined. The Pax3 Splotch-delayed (Pax3Sp-d) mouse model of SB is one of a very few mouse SB models that survives to late stages of gestation. Through analysis of Pax3Sp-d mutants we sought to define how altered bladder innervation in SB might arise by tracing sacral neural crest (NC) development, pelvic ganglia neuronal differentiation, and assessing bladder nerve fiber density. In Pax3Sp-d/Sp-d fetal mice we observed delayed migration of Sox10+ NC-derived progenitors (NCPs), deficient pelvic ganglia neurogenesis, and reduced density of bladder wall innervation. We further combined NC-specific deletion of Pax3 with the constitutive Pax3Sp-d allele in an effort to generate viable Pax3 mutants to examine later stages of bladder innervation and postnatal bladder function. Neural crest specific deletion of a Pax3 flox allele, using a Sox10-cre driver, in combination with a constitutive Pax3Sp-d mutation produced postnatal viable offspring that exhibited altered bladder function as well as reduced bladder wall innervation and altered connectivity between accessory ganglia at the bladder neck. Combined, the results show that Pax3 plays critical roles within sacral NC that are essential for initiation of neurogenesis and differentiation of autonomic neurons within pelvic ganglia.
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影响因子：
2
作者：
Deng N;Thirumavalavan N;Beilan JA;Tatem AJ;Hockenberry MS;Pastuszak AW;Lipshultz LI
通讯作者：
Lipshultz LI
影响因子：
2.7
作者：
Dude, Carolynn M.;Kuan, C. -Y. Kelly;Bradshaw, James R.;Greene, Nicholas D. E.;Relaix, Frederic;Stark, Michael R.;Baker, Clare V. H.
通讯作者：
Baker, Clare V. H.
畜牧业对C57BL/6J雄性小鼠无效现场测定结果的影响。
影响因子：
2
作者：
Keil, Kimberly P.;Abler, Lisa L.;Altmann, Helene M.;Bushman, Wade;Marker, Paul C.;Li, Lingjun;Ricke, William A.;Bjorling, Dale E.;Vezina, Chad M.
通讯作者：
Vezina, Chad M.
DOI：
10.1038/nrdp.2015.7
发表时间：
2015-04-30
期刊：
Nature reviews. Disease primers
影响因子：
--
作者：
Copp AJ;Adzick NS;Chitty LS;Fletcher JM;Holmbeck GN;Shaw GM
通讯作者：
Shaw GM
影响因子：
6.6
作者：
CASS, AS;SPENCE, BR
通讯作者：
SPENCE, BR