- When trying to understand the biological differences that lead to defects in cranial neural tube closure, researchers have looked at genomic differences that create variation in Shh expression 
- Researchers found that expanded Shh expression (and subsequent failure to curve the cranial neural plate) is caused by changes to the transcription factors Gli2/ Gli3 (specific regions of a gene that control the speed/degree of transcription of genetic information)  
- Changes to Gli2/Gli3 is theorized to cause the loss of the expression of the morphogen "Noggin" (antagonist of BMP), which is responsible for bending of the spinal neural plate, and has previously been documented as causing exencephaly when when lost 

Molecular Changes in the Sonic Hedgehog/ Apical Constriction Relationship 

- The difference between cells that undergo apical constriction (lateral cells) and those that experience apical expansion (medial cells) is determined by their proximity to Shh signaling 
- This is based on existing patterns of Shh signaling, which is high at the midline, and decreases gradually as it reaches the lateral points 
- This is further supported by previous studies that altered Shh signaling, and found that the midline cells faced issues in forming its normal cell shape 
- Therefore, high levels of Shh produce short and expanded cell shape, while low levels of Shh produce tall and constricted cell shape 

Smith College

- Recent research has elucidated some of the mechanisms that may be involved in cranial neural tube closure, which includes apical constriction of lateral cells within the midbrain, while there is sustained apical expansion for midline cells 
- These processes are regulated by Shh signaling, and is therefore a vital morphogen factor in cranial neural tube cell remodeling, and subsequent closure  

Mechanisms of Cranial Neural Tube Closure 

Brooks, E. R., Islam, M. T., Anderson, K. V., & Zallen, J. A. (2020). Sonic hedgehog signaling directs patterned cell remodeling during cranial neural tube closure. eLife, 9, e60234. https://doi.org/10.7554/eLife.60234

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