First-ever transgenic zebrafish study in Pakistan reveals important aspects of gene regulation



 Understanding the presence and significance of introns (apparently  non-functional or junk DNA) in the human genome has always been a  hot topic for evolutionary developmental biologists. ‘Comparative and  evolutionary genomics laboratory’ in National Centre for Bioinformatics,  Quaid-i-Azam University, Islamabad, is considered to be pioneer in the  field of “Human Gene Regulation” in Pakistan.A PhD scholar, Rashid  Minhas, from this lab has recently published an interesting story, as  the lead author,entitled “Cis-regulatory control of human GLI2 expression in the developing neural tube and limb bud”. This article published in the one of the prestigious Wiley journal, Developmental Dynamics, (DOI: 10.1002/DVDY.24266) reveals how conserved non-coding regions, called 'CNEs', docked in the introns of GLI2 gene, when tested using zebrafish as a model, act as tissue-specific enhancers.

GLI2 is a highly conserved developmental gene in vertebrates, and is shown in various studies to play a very important role during embryogenesis. Exonic mutations in this gene can cause several developmental defects like defective anterior pituitary formation, pan-hypo pituitarism, and forebrain anomalies, represented by typical holoprosencephaly and holoprosencephaly-like phenotypes and postaxial polydactyly. GLI2 has also been implicated to have a significant role in skin cancers, including basal cell carcinoma, and other cancers like: breast and prostate. To address the gene regulation of this important gene, Comparative and evolutionary genomics group (NCB) employed a combination of computational and functional assays to segregate its cis-regulatory modules. They selected zebrafish as an in vivo model, to test the functionality of these human-fish conserved cis-regulatory modules of GLI2.

In this study, the authors show how injecting the apparently junk DNA in zebrafish embryos, upregulates a reporter gene in several anatomical domains of this interesting little creature, especially in the central nervous system and fins.These findings open new avenues, to understand the structural, architectural and evolutionary dynamics of GLI2, and its participation in human inherited diseases.To date, it is the first-ever scientific study based on transgenic zebrafish models from Pakistan.