Development of adrenal chromaffin cells in Sf1 heterozygous mice

Abstract

Adrenal medullary chromaffin cells are derivatives of the neural crest and are widely believed to share a common sympathoadrenal (SA) progenitor with sympathetic neurons. For decades, the adrenal cortical environment was assumed to be essential for channelling SA progenitors towards an endocrine chromaffin cell fate. Our recent analysis of steroidogenic factor 1(Sf1) -/- mice, which lack an adrenal cortex, has challenged this view: in Sf1 -/- mice chromaffin cells migrate to the correct "adrenal" location and undergo largely normal differentiation. In contrast to Sf1 homozygous mutants, heterozygous animals have an adrenal cortex, which, however, is smaller than in wildtype littermates. We show here that the Sf1 +/- adrenal cortical anlagen attract normal numbers of chromaffin progenitor cells into their vicinity by embryonic day 13.5 (E13.5). Two days later, however, only a few scattered cells with highly immature features have immigrated into the adrenal cortex, whereas the remainder form a coherent cell assembly ectopically located at the medial surface of the gland. These cells appear more mature than the scattered intracortical chromaffin progenitors and express the adrenaline synthesizing enzyme PNMT with a delay of 1 day in comparison with wildtype littermates. Nevertheless, chromaffin progenitor cells undergo a numerical reduction of approximately 30% by E17.5. Together, our data suggest that normal adrenocortical development is critical for the correct immigration of chromaffin progenitors into the cortical anlagen, for the timing of PNMT expression and for the regulation of chromaffin cell numbers.

Expression patterns of the Wtx/Amer gene family during mouse embryonic development

“…9(i)). These cells very likely correspond to neural crest derived adrenal medullary chromaffin cells, which could be confirmed by a co‐staining using tyrosine hydroxylase as a marker (Lohr et al,2006).…”

Fibronectin mediates correct positioning of the interrenal organ in zebrafish

“…In the adult mice, the transgenic Ad4BP/SF‐1 expression leads to eccentric chromaffin cell location and thus a disorganized adrenal organ architecture. Similarly, reduced size of the adrenal cortical anlagen in Ad4BP/SF‐1 heterozygous mice leads to unsuccessful immigration of chromaffin progenitors into the cortical anlagen (Lohr et al, ). On the other hand, differentiation of the chromaffin cell lineage was not affected upon a lack of the adrenal cortex in Ad4BP/SF‐1 homozygous mice (Gut et al, ).…”

Development of the Autonomic Nervous System: Clinical Implications

“…40,41,95 They then begin differentiating into chromaffin cells, with a subset turning on PNMT and expressing adrenalin. 96,97 Like sympathetic neurons, adrenal chromaffin development is dependent on BMP signaling, Phox2b, and Mash1/Ascl. 41,44,46 Neural crest-derived glial cells in the form of sustentacular cells are also present in the adrenal medulla and may act as stem-like cells.…”