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This evolutionarily conserved trait, shared by different animal species, is supported by two mechanisms: the object tracking system (OTS) for small sets and the approximate number system (ANS) for larger quantities. Although historically viewed as distinct, these systems interact dynamically; their disruption is implicated in developmental dyscalculia and disorders such as Williams\u2013Beuren syndrome (WBS), a chromosome microdeletion characterised by marked numerical and visuospatial deficits. Here, we synthesise neurobiological advances to provide an integrative perspective on the neural substrates of number sense. Field studies provide ecological validity, while laboratory procedures offer tighter precision; together, they illuminate the biological foundations of numerical cognition. Although number sense is conserved, human studies indicate only moderate heritability likely reflecting directional selection. Nonetheless, genetic findings converge on neurodevelopmental and synaptic mechanisms. Zebrafish (\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Danio rerio<\/jats:italic>\n                    <\/jats:styled-content>\n                    ) offer a powerful platform to bridge genes, circuits and behaviour. For instance, manipulating zebrafish genes linked to WBS reveals gene\u2010specific effects on quantity processing. At the neural level, numerical cognition is largely supported by specialised number\u2010selective neurons. Whole\u2010brain calcium imaging in larval zebrafish demonstrates that these neurons emerge by 3\u2009days postfertilisation and follow a trajectory where representations of small numerosities precede larger ones. Altogether, integrating genetic, behavioural and circuit\u2010level approaches provides a powerful framework for uncovering conserved mechanisms of numerosity supporting higher\u2010level cognitive functions, including mathematics.\n                  <\/jats:p>","DOI":"10.1111\/ejn.70506","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T05:28:26Z","timestamp":1776835706000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Exploring the Neural Substrates of Number Sense: A Perspective on Genetics, Behaviour and Neural Circuity"],"prefix":"10.1111","volume":"63","author":[{"given":"Mirko","family":"Zanon","sequence":"first","affiliation":[{"name":"Center for Mind\/Brain Sciences University of Trento  Rovereto Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline\u00a0H.","family":"Brennan","sequence":"additional","affiliation":[{"name":"School of Biological and Behavioural Sciences Queen Mary University of London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria\u00a0Elena\u00a0Miletto","family":"Petrazzini","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences University of Padova  Padova Italy"},{"name":"Department of General Psychology University of Padova  Padova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose\u00a0V.","family":"Torres\u2010P\u00e9rez","sequence":"additional","affiliation":[{"name":"Departament de Biologia Cel\u00b7lular, Biologia Funcional i Antropologia F\u00edsica Universitat de Val\u00e8ncia  Val\u00e8ncia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,21]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10071-024-01888-0"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2014.04.027"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10071-008-0140-9"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2334"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1098\/rsos.242138"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10071-019-01238-5"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1163\/1568539X-00003391"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0096374"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.1162\/089892900561959"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.112772"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2022.110472"},{"key":"e_1_2_14_13_1","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2016.0508"},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anbehav.2014.05.012"},{"key":"e_1_2_14_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2020.11.039"},{"key":"e_1_2_14_16_1","doi-asserted-by":"publisher","DOI":"10.4324\/9781315807393"},{"key":"e_1_2_14_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2011.12.021"},{"key":"e_1_2_14_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/jopy.12186"},{"key":"e_1_2_14_19_1","doi-asserted-by":"publisher","DOI":"10.4324\/9781315538112"},{"key":"e_1_2_14_20_1","volume-title":"Can Fish Count? 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