Developmental time window model for cranial NTDs such as exencephaly. (A) A schematic representation of NTC in control and apoptosis-deficient embryos. (i and ii) Transverse (i) and dorsal (ii) views of MHNP. The types of apoptotic cells are as shown in Fig. 3 D. Apoptosis helps smooth the morphological changes of the neural plate (blue arrows). Surface ectoderm may provide forces that cause the neural plate to flip and bend (green arrows). As a consequence of the reduced bending in the absence of apoptosis (pink arrows), closure progressed more slowly (shown by small red arrows in ii). The neural plate is shown in purple, and the surface ectoderm is shown in green. (B and C) Developmental time window model for the cranial NTC. (B) NTC must be completed by a developmental deadline (about somite stage 20), when forces incompatible with NTC may arise. Apoptosis helps smooth the progression of NTC, allowing it to be completed by the deadline. (C) Even when closure is delayed, the embryo can develop without NTDs, as long as NTC can be completed before the deadline (case indicated by dotted arrow). However, if closure is not completed by the deadline, cranial NTC ends in failure to close at the MHNP, resulting in cranial NTDs such as exencephaly.