SMAD6-mediated modulation of BMP/TGF-β signaling disrupts midbrain growth in chick embryos

[摘要] Bone morphogenetic proteins (BMPs) play important roles in dorsal spinal cord patterning. Their presence in the roof plate of the midbrain suggests that BMP-related signaling may also contribute to dorsal midbrain development. However, whether BMP/TGF-β-associated SMAD-dependent signaling contributes to dorsal midbrain growth remains unclear. We examined this question in chick embryos by misexpressing components of BMP/TGF-β-associated signaling pathways. BMP4 overexpression did not affect midbrain growth, whereas GDF7 overexpression reduced midbrain growth. Expression of a truncated dominant-negative BMP receptor type 1b had no detectable effect on midbrain size. Ectopic expression of SMAD6, an intracellular inhibitor of BMP/TGF-β-associated SMAD-dependent signaling, significantly reduced midbrain size, which correlated with reduced mitotic activity in SMAD6-overexpressing cells. SMAD6 overexpression was also associated with low-penetrance changes in mesencephalic trigeminal nucleus (MTN) axon trajectories. These results support a contribution of SMAD-dependent signaling pathways to early dorsal midbrain growth.

[发布日期] 2026-09-11

[关键词] Midbrain development;BMP signaling;TGF-β signaling;SMAD6;GDF7;Chick embryo