Good day, Ma’am Leonardo!
Our group is very grateful for your positive comments regarding our presentation.
Here are our responses to your questions:
1. Can you elaborate on the mechanism by which NOGGIN regulates BMP4?
NOG, otherwise known as Noggin, is a gene that codes for the production of a dimeric glycoprotein with the same name. The Noggin protein forms a homodimer that shares a similar structure with the BMP ligands cysteine-knot fold tertiary form that is known to include two beta-strand loops. What differentiates noggin from BMP4, however, is that it also contains a sequence that is composed of short alpha-helices. This structure effectively allows Noggin to directly bind with BMP4 and block the binding sites that are supposedly reserved for receptors. In summary, Noggin can regulate BMP4 by directly binding to them, which consequently prevents them from interacting and transmitting their signal to their target receptor. This puts a halt to the signal transduction pathway.
Reference: Zimmerman, L. B., De Jesús-Escobar, J. M., & Harland, R. M. (1996). The Spemann Organizer Signal noggin Binds and Inactivates Bone Morphogenetic Protein 4. Cell, 86(4), 599–606. https://doi.org/10.1016/S0092-8674(00)80133-6
2. Give the possible effects of NMYC and CDH7 on the development of the trachea and the esophagus.
N-myc proto-oncogene or NMYC is a transcription factor mainly expressed during fetal brain development (Knoepfler et al., 2002). Expression of NMYC is highly critical, thus, defects in this gene usually lead to life-threatening diseases. The most common type of anomaly concerning NMYC is haploinsufficiency where the other allele encoding for the NMYC is either mutated or completely deleted (van Bokhoven et al., 2005). NMYC haploinsufficiency usually manifests as a congenital malformation syndrome known as the Feingold syndrome which presents several symptoms including esophageal atresia and tracheoesophageal fistula (EA/TEF) (van Bokhoven et al., 2005).
CDH7 or chromodomain helicase DNA binding (CDH) is necessary during early embryonic development as it directly affects chromatin structure and gene expression (van Bokhoven et al., 2005). Like NMYC, the most common type of CDH7 anomaly is haploinsufficiency. CDH7 haploinsufficiency usually manifests as a developmental disorder known as the CHARGE syndrome which leads to malformations of several organs including the esophagus, thus, leading to EA (van Bokhoven et al., 2005).
References:
Brunner, H. G., & Bokhoven, H. van. (2005). Genetic players in esophageal atresia and tracheoesophageal fistula. Current Opinion in Genetics & Development, 15(3), 341–347. https://doi.org/10.1016/j.gde.2005.04.010
Knoepfler, P. S., Cheng, P. F., & Eisenman, R. N. (2002). N-myc is essential during neurogenesis for the rapid expansion of progenitor cell populations and the inhibition of neuronal differentiation. Genes & Development, 16(20), 2699–2712. https://doi.org/10.1101/gad.1021202
van Bokhoven, H., Celli, J., van Reeuwijk, J., Rinne, T., Glaudemans, B., van Beusekom, E., Rieu, P., Newbury-Ecob, R. A., Chiang, C., & Brunner, H. G. (2005). MYCN haploinsufficiency is associated with reduced brain size and intestinal atresias in Feingold syndrome. Nature Genetics, 37(5), 465–467. https://doi.org/10.1038/ng1546
