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Embryological, molecular and genetic data indicate that head and trunk development are significantly different, suggesting that the transition into the trunk formation stage involves major changes in regulatory gene networks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We explored those regulatory changes by generating differential interaction networks and chromatin accessibility profiles from the posterior epiblast region of mouse embryos at embryonic day (E)7.5 and E8.5. We observed changes in various cell processes, including several signaling pathways, ubiquitination machinery, ion dynamics and metabolic processes involving lipids that could contribute to the functional switch in the progenitor region of the embryo. We further explored the functional impact of changes observed in Wnt signaling associated processes, revealing a switch in the functional relevance of Wnt molecule palmitoleoylation, essential during gastrulation but becoming differentially required for the control of axial extension and progenitor differentiation processes during trunk formation. We also found substantial changes in chromatin accessibility at the two developmental stages, mostly mapping to intergenic regions and presenting differential footprinting profiles to several key transcription factors, indicating a significant switch in the regulatory elements controlling head or trunk development. Those chromatin changes are largely independent of retinoic acid, despite the key role of this factor in the transition to trunk development. We also tested the functional relevance of potential enhancers identified in the accessibility assays that reproduced the expression profiles of genes involved in the transition. Deletion of these regions by genome editing had limited effect on the expression of those genes, suggesting the existence of redundant enhancers that guarantee robust expression patterns.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This work provides a global view of the regulatory changes controlling the switch into the axial extension phase of vertebrate embryonic development. It also revealed mechanisms by which the cellular context influences the activity of regulatory factors, channeling them to implement one of several possible biological outputs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12915-023-01675-2","type":"journal-article","created":{"date-parts":[[2023,8,8]],"date-time":"2023-08-08T07:02:34Z","timestamp":1691478154000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Regulatory changes associated with the head to trunk developmental transition"],"prefix":"10.1186","volume":"21","author":[{"given":"Patr\u00edcia","family":"Duarte","sequence":"first","affiliation":[]},{"given":"Rion","family":"Brattig Correia","sequence":"additional","affiliation":[]},{"given":"Ana","family":"N\u00f3voa","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9744-0912","authenticated-orcid":false,"given":"Mois\u00e9s","family":"Mallo","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2023,8,8]]},"reference":[{"key":"1675_CR1","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1387\/ijdb.052095cs","volume":"50","author":"CD Stern","year":"2006","unstructured":"Stern CD, Charite J, Deschamps J, Duboule D, Durston AJ, Kmita M, et al. 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All experiments conducted on animals followed the Portuguese (Portaria 1005\/92) and European (Directive 2010\/63\/EU) legislations concerning housing, husbandry, and welfare. The project was reviewed and approved by the Ethics Committee of Instituto Gulbenkian de Ci\u00eancia and by the Portuguese National Entity, Direc\u00e7\u00e3o Geral de Alimenta\u00e7\u00e3o e Veterin\u00e1ria (license reference 014308).This work does not include human samples or data from human patients.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"170"}}