Editing Evolutionary developmental biology (section)

===The embryo's regulatory networks===
{{Further|Regulation of gene expression|Transcriptional regulation}}

[[File:Gene Regulatory Network.jpg|thumb|upright=1.6|A [[gene regulatory network]]]]

The protein products of the regulatory toolkit are reused not by duplication and modification, but by a complex mosaic of [[pleiotropy]], being applied unchanged in many independent developmental processes, giving pattern to many dissimilar body structures.<ref name=Carroll_2008/> The loci of these pleiotropic toolkit genes have large, complicated and modular [[cis-regulatory element]]s. For example, while a non-pleiotropic [[rhodopsin]] gene in the fruit fly has a cis-regulatory element just a few hundred [[base pair]]s long, the pleiotropic [[eyeless]] cis-regulatory region contains 6 cis-regulatory elements in over 7000 base pairs.<ref name=Carroll_2008/> The [[gene regulatory network|regulatory networks]] involved are often very large. Each regulatory protein controls "scores to hundreds" of cis-regulatory elements. For instance, 67 fruit fly transcription factors controlled on average 124 target genes each.<ref name=Carroll_2008/> All this complexity enables genes involved in the development of the embryo to be switched on and off at exactly the right times and in exactly the right places. Some of these genes are structural, directly forming enzymes, tissues and organs of the embryo. But many others are themselves regulatory genes, so what is switched on is often a precisely-timed cascade of switching, involving turning on one developmental process after another in the developing embryo.<ref name=Carroll_2008/>

[[File:Drosophila early embryo protein gradients.svg|thumb|upright=1.2|left|Gene product distributions along the long axis of the early embryo of a [[Drosophila melanogaster|fruit fly]]]]

Such a cascading regulatory network has been studied in detail in the [[Drosophila embryogenesis|development of the fruit fly embryo]]. The young embryo is oval in shape, like a [[rugby ball]]. A small number of genes produce [[messenger RNA]]s that set up concentration gradients along the long axis of the embryo. In the early embryo, the ''[[bicoid]]'' and ''hunchback'' genes are at high concentration near the anterior end, and give pattern to the future head and thorax; the ''caudal'' and ''[[nanos (gene)|nanos]]'' genes are at high concentration near the posterior end, and give pattern to the hindmost abdominal segments. The effects of these genes interact; for instance, the Bicoid protein blocks the translation of ''caudal''{{'s}} messenger RNA, so the Caudal protein concentration becomes low at the anterior end. Caudal later switches on genes which create the fly's hindmost segments, but only at the posterior end where it is most concentrated.<ref name="Russel">{{Cite book |last=Russel |first=Peter |title=iGenetics: a molecular approach |publisher=Pearson Education |year=2010 |isbn=978-0-321-56976-9 |pages=564–571}}</ref><ref name="Rivera">{{Cite journal |last=Rivera-Pomar |first=Rolando |last2=Jackle, Herbert |year=1996 |title=From gradients to stripes in Drosophila embryogenesis: Filling in the gaps |journal=Trends in Genetics |volume=12 |issue=11 |pages=478–483 |doi=10.1016/0168-9525(96)10044-5 |pmid=8973159}}</ref>

[[File:Gap gene expression.svg|thumb|upright=0.8|[[Gap gene]]s in the fruit fly are switched on by genes such as ''[[bicoid]]'', setting up stripes across the embryo which start to pattern the body's segments.]]

The Bicoid, Hunchback and Caudal proteins in turn regulate the transcription of [[gap gene]]s such as ''giant'', ''knirps'', ''Krüppel'', and ''tailless'' in a striped pattern, creating the first level of structures that will become segments.<ref name="Nusslein" /> The proteins from these in turn control the [[pair-rule gene]]s, which in the next stage set up 7 bands across the embryo's long axis. Finally, the segment polarity genes such as ''[[engrailed (gene)|engrailed]]'' split each of the 7 bands into two, creating 14 future segments.<ref name=Russel/><ref name=Rivera/>

This process explains the accurate conservation of toolkit gene sequences, which has resulted in deep homology and functional equivalence of toolkit proteins in dissimilar animals (seen, for example, when a mouse protein controls fruit fly development). The interactions of transcription factors and cis-regulatory elements, or of signalling proteins and receptors, become locked in through multiple usages, making almost any mutation deleterious and hence eliminated by natural selection.<ref name=Carroll_2008/>

The mechanism that sets up every [[animal]]'s front-back axis is the same, implying a common ancestor. There is a similar mechanism for the back-belly axis for [[bilateria]]n animals, but it is reversed between [[arthropod]]s and [[vertebrate]]s.<ref>{{Cite journal |last=De Robertis |first=Eddy |last2=Sasai |first2=Yoshiki |year=1996 |title=A common plan for dorsoventral patterning in Bilateria |journal=Nature |volume=380 |issue=6569 |pages=37–40 |bibcode=1996Natur.380...37D |doi=10.1038/380037a0 |pmid=8598900 |s2cid=4355458}}</ref> Another process, [[gastrulation]] of the embryo, is driven by [[Myosin II]] molecular motors, which are not conserved across species. The process may have been started by movements of sea water in the environment, later replaced by the evolution of tissue movements in the embryo.<ref>{{Cite journal |last=Farge |first=Emmanuel |year=2003 |title=Mechanical induction of twist in the Drosophila foregut/stomodeal primordium |journal=Current Biology |volume=13 |issue=16 |pages=1365–1377 |doi=10.1016/s0960-9822(03)00576-1 |pmid=1293230 |doi-access=free}}</ref><ref>{{Cite journal |last=Nguyen |first=Ngoc-Minh |last2=Merle |first2=Tatiana |display-authors=etal |year=2022 |title=Mechano-biochemical marine stimulation of inversion, gastrulation, and endomesoderm specification in multicellular Eukaryota |journal=Frontiers in Cell and Developmental Biology |volume=10 |page=992371 |doi=10.3389/fcell.2022.992371 |pmc=9754125 |pmid=36531949 |doi-access=free}}</ref>