Lack of an adrenal cortex in Sf1 mutant mice is compatible with the generation and differentiation of chromaffin cells
Lack of an adrenal cortex in Sf1 mutant mice is compatible with the generation and differentiation of chromaffin cells
复制标题
DOI：
10.1242/dev.02052
复制
发表时间：
2005-10-01
期刊：
影响因子：
4.6
通讯作者：
Unsicker, K
中科院分区：
文献类型：
--
作者：
Gut, P;Huber, K;Unsicker, K
人们认为，神经嵴来源的交感肾上腺（SA）祖细胞分化为交感神经元和神经内分泌肾上腺嗜铬细胞的过程已基本被了解。对分离的 SA 祖细胞的体外研究表明，嗜铬细胞的分化主要取决于肾上腺皮质细胞提供的糖皮质激素。然而，对缺乏糖皮质激素受体基因的小鼠的分析表明，这些小鼠的肾上腺嗜铬细胞大多正常发育。尚未确定来自肾上腺皮质的可能促进嗜铬细胞确定和分化的替代信号。因此，我们使用缺乏核孤儿受体类固醇生成因子-1（SF1）的小鼠（缺乏肾上腺皮质细胞和性腺）来研究嗜铬细胞表型是否可以在没有肾上腺皮质的情况下发育。我们发现，在 Sf1(-/-) 小鼠中，典型的嗜铬细胞在邻近肾上交感神经节的肾上区域正确组装。这些细胞表现出嗜铬细胞的大部分特征，包括典型的大嗜铬颗粒。在胚胎日(E)13.5和E17.5时，与野生型相比，Sf1(-/-)嗜铬细胞的数量减少了约50%。这种表型不能用E12.5以上存活率或细胞增殖降低来解释。然而，在 E12.5 时，Sf1(-/-) 小鼠的“肾上腺”区域已被较少的 PHOX2B(+) 和 TH+ SA 细胞以及 SOX10(+) 神经嵴细胞占据。我们的结果表明，皮质线索对于确定嗜铬细胞的命运并不重要，但可能是SA祖细胞正确迁移到肾上腺原基和/或在肾上腺原基上定植所必需的。
The diversification of neural-crest-derived sympathoadrenal (SA) progenitor cells into sympathetic neurons and neuroendocrine adrenal chromaffin cells was thought to be largely understood. In-vitro studies with isolated SA progenitor cells had suggested that chromaffin cell differentiation depends crucially on glucocorticoids provided by adrenal cortical cells. However, analysis of mice lacking the glucocorticoid receptor gene had revealed that adrenal chromaffin cells develop mostly normally in these mice. Alternative cues from the adrenal cortex that may promote chromaffin cell determination and differentiation have not been identified. We therefore investigated whether the chromaffin cell phenotype can develop in the absence of an adrenal cortex, using mice deficient for the nuclear orphan receptor steroidogenic factor-1 (SF1), which lack adrenal cortical cells and gonads. We show that in Sf1(-/-) mice typical chrornaffin cells assemble correctly in the suprarenal region adjacent to the suprarenal sympathetic ganglion. The cells display most features of chromaffin cells, including the typical large chromaffin granules. Sf1(-/-) chromaffin cells are numerically reduced by about 50% compared with the wild type at embryonic day (E) 13.5 and E17.5. This phenotype is not accounted for by reduced survival or cell proliferation beyond E12.5. However, already at E12.5 the 'adrenal' region in Sf1(-/-) mice is occupied by fewer PHOX2B(+) and TH+ SA cells as well as SOX10(+) neural crest cells. Our results suggest that cortical cues are not essential for determining chromaffin cell fate, but may be required for proper migration of SA progenitors to and/or colonization of the adrenal anlage.