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In hybrids, the placenta is a hotspot for genetic and epigenetic incompatibilities that preferentially affect males. Whether the hybrid brain is similarly affected is an open question. We evaluated the effects of hybridization and placental dysregulation on neural gene expression (embryonic, juvenile, adult) and behaviour (juvenile, adult) in a cross between the house mouse (Mus musculus domesticus) and Algerian mouse (Mus spretus), in which transgressive expression of imprinted and X-linked genes is a prominent feature of undersized F1 male placentas. In hybrid hypothalamus, transgressive expression was mainly embryonic and highly male-biased. Although fewer genes were dysregulated in hybrid male embryonic hypothalamus relative to placenta, we infer a similar genetic architecture involving X\u2013IG incompatibilities and incompatibilities between IGs and autosomal interaction partners. Hybrids had heightened anxiety-like behaviour and reduced activity relative to parental species, with a tendency towards larger behavioural differences in adult males. As the first study to our knowledge to characterize the effects of interspecific hybridization on neural gene expression and behaviour in a mammal, this work extends the scope of phenotypes impacted by intrinsic incompatibilities and demonstrates that the brain obeys Haldane\u2019s rule.<\/jats:p>","DOI":"10.1098\/rspb.2025.3060","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:19:27Z","timestamp":1779236367000},"source":"Crossref","is-referenced-by-count":2,"title":["Haldane\u2019s rule in the developing brain: X-linked and imprinted genes contribute to male-biassed transgressive expression in hybrid mice"],"prefix":"10.1098","volume":"293","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0681-0392","authenticated-orcid":false,"given":"Lena","family":"Ar\u00e9valo","sequence":"first","affiliation":[{"name":"Instituto Nacional de Investigaci\u00f3n y Tecnolog\u00eda Agraria y Alimentaria (INIA-CSIC) 1 , ,","place":["Madrid 28040, Spain"],"department":["Department of Animal Reproduction"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7660-9814","authenticated-orcid":false,"given":"Polly","family":"Campbell","sequence":"additional","affiliation":[{"name":"University of California Riverside 2 , , ,","place":["Riverside, CA 92521, USA"],"department":["Department of Evolution, Ecology, and Organismal Biology"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"175","published-online":{"date-parts":[[2026,5,20]]},"reference":[{"key":"2026051920192053500_R1","doi-asserted-by":"crossref","first-page":"15237","DOI":"10.1073\/pnas.1106022108","article-title":"Placental protection of the fetal brain during short-term food deprivation","volume":"108","author":"Broad","year":"2011","journal-title":"Proc. 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