Misner Rachel, Reilein Amy, Kalderon Daniel
Department of Biological Sciences, Columbia University, New York, USA.
bioRxiv. 2025 May 13:2025.05.08.652870. doi: 10.1101/2025.05.08.652870.
Follicle Stem Cells (FSCs) in the germarium of a Drosophila melanogaster ovary are maintained through independent regulation of division and differentiation. Adult FSCs can become proliferative Follicle Cells (FCs) to the posterior, or quiescent Escort Cells (ECs) to the anterior. Graded extracellular Hedgehog (Hh) and Wnt signals emanate from cells anterior to FSCs (Cap Cells and ECs) to guide these behaviors together with an inverse JAK-STAT pathway stimulated by ligand from a more posterior source (polar FCs). Here we used lineage analyses to investigate the role of those signals in the development of ECs, FSCs and FCs from a common set of precursors during pupation. Previous studies found that the most anterior precursors divide slowest, with quiescence spreading to all future ECs from the anterior, FSCs are specified simply by their location at eclosion, and the first FCs derive from a group of cells that accumulates posterior to the developing germline over the first 48h of pupation. We now show that the latter cells derive from migration of precursors out of the developing germarium. We also found that Wnt pathway activity favored conversion of precursors to more anterior adult derivatives, while JAK-STAT pathway activity favored posterior outcomes. Wnt pathway activity increased over the first 48h and maintained a graded pattern throughout pupation, terminating at the anterior extent of FC specification, commensurate with Wnt pathway activity continuously opposing FC formation. JAK-STAT pathway activity was consistently lowest in anterior cells, indicating a posterior source early in pupation prior to formation of the first polar FCs. Precursor division was promoted by JAK-STAT signaling and also by Hh signaling, acting through transcriptional induction of . Faster division favored a precursor becoming an FSC, as seen for FSC lineage maintenance in adults.
果蝇卵巢生殖腺中的卵泡干细胞（FSCs）通过分裂和分化的独立调节得以维持。成年FSCs可向后分化为增殖性卵泡细胞（FCs），或向前分化为静止的护送细胞（ECs）。从FSCs前方的细胞（帽细胞和ECs）发出的梯度细胞外Hedgehog（Hh）和Wnt信号，与来自更后方来源（极性FCs）的配体刺激的反向JAK-STAT途径共同引导这些行为。在这里，我们使用谱系分析来研究这些信号在化蛹期间从一组共同前体发育为ECs、FSCs和FCs过程中的作用。先前的研究发现，最前方的前体分裂最慢，静止状态从前方扩散到所有未来的ECs，FSCs仅由羽化时的位置决定，并且第一批FCs来自化蛹后48小时内在发育中的生殖系后方积累的一组细胞。我们现在表明，后一组细胞源自前体从发育中的生殖腺迁移出来。我们还发现，Wnt信号通路活性有利于前体转化为更靠前的成年衍生物，而JAK-STAT信号通路活性有利于向后的结果。Wnt信号通路活性在最初的48小时内增加，并在整个化蛹过程中保持梯度模式，在FC特化的前方范围终止，这与Wnt信号通路活性持续对抗FC形成相一致。JAK-STAT信号通路活性在前部细胞中始终最低，表明在第一批极性FCs形成之前的化蛹早期有一个后方来源。前体分裂受到JAK-STAT信号传导的促进，也受到Hh信号传导的促进，后者通过转录诱导起作用。更快的分裂有利于前体成为FSC，这在成年FSC谱系维持中可见。
