Morrison J A, Pushel I, McLennan R, McKinney M C, Gogol M M, Scott A, Krumlauf R, Kulesa P M
bioRxiv. 2024 Nov 6:2024.11.06.622355. doi: 10.1101/2024.11.06.622355.
A core framework of the gene regulatory network (GRN) governing neural crest (NC) cell development has been generated by integrating separate inputs from diverse model organisms rather than direct comparison. This has limited insights into the diversity of genes in the NC cell GRN and extent of conservation of newly identified transcriptional signatures in cell differentiation and invasion. Here, we address this by leveraging the strengths and accessibility of the avian embryo to precise developmental staging by egg incubation and use an integrated analysis of chick (HH13) and mouse (E9.5) embryo tissue samples collected during NC cell migration into pharyngeal arches 1-2 (PA1 and PA2). We successfully identify a cluster of NC cells containing both mouse and chick cells that share expression of , , , and , and distinct genes that lack known conserved roles in NC. Importantly, we discovered a cluster of cells exhibiting a conserved transcriptional signature associated with the NC cell migratory wavefront in both mouse and chick, including KAZALD1, BAMBI, DES, and GPC3. We confirm their expression is restricted to leader mouse NCs by multiplexed FISH. Together, these data offer novel insights into the transcriptional programs that underlie NC cell migration and establish the foundation for future comparative functional analyses.
通过整合来自不同模式生物的独立输入而非直接比较,生成了一个控制神经嵴(NC)细胞发育的基因调控网络(GRN)核心框架。这限制了对NC细胞GRN中基因多样性以及细胞分化和侵袭中新鉴定转录特征的保守程度的深入了解。在此,我们利用鸡胚通过卵孵化实现精确发育分期的优势和易操作性来解决这一问题,并对NC细胞迁移至咽弓1-2(PA1和PA2)期间收集的鸡(HH13)和小鼠(E9.5)胚胎组织样本进行综合分析。我们成功鉴定出一群同时包含小鼠和鸡细胞的NC细胞簇,它们共享 、 、 和 的表达,以及在NC中缺乏已知保守作用的独特基因。重要的是,我们发现了一群在小鼠和鸡中均表现出与NC细胞迁移波前相关的保守转录特征的细胞簇,包括KAZALD1、BAMBI、DES和GPC3。我们通过多重荧光原位杂交证实它们的表达仅限于小鼠NC的先导细胞。这些数据共同为NC细胞迁移背后的转录程序提供了新的见解,并为未来的比较功能分析奠定了基础。