{"doi":"10.1242/dev.204594","title":"In preprints: giving the developing brain the energy it needs","abstract":"Metabolism is increasingly appreciated for its active role in tissue development during embryogenesis, particularly its discrete instruction in brain growth and formation. Catabolic programs are essential for the breakdown of nutrients to provide energy for anabolic processes that construct macromolecules and cell structures required for tissue expansion and organization (Rajan and Fame, 2024). Nutrient availability and environmental factors influence the bioenergetic state of developing cells, and instruct cellular and tissue-specific niches throughout embryogenesis (Traxler et al., 2021; Andrews and Pearson, 2024). Intracellular metabolism uses external cues from the maternal and embryonic environments to modify gene expression through epigenetic modifications and genomic accessibility (Reid et al., 2017; Sánchez-Ramírez et al., 2024). Therefore, assessing the relationship between the cell metabolome and developmental programs can provide insights into the mechanisms that regulate proliferation, differentiation and maturation during brain formation.A recent preprint by Saha and colleagues highlights the importance of nutrient availability for brain development by examining the effects of methionine restriction on cellular- and tissue-level changes (Saha et al., 2024 preprint). Methionine, in conjunction with other metabolites, is interconnected with numerous metabolic pathways and signaling cascades that coordinate cell function and developmental programs (Sanderson et al., 2019). This study evaluated the impact of maternal dietary methionine restriction in mice from embryonic day (E) 9.5 throughout gestation or exclusively during neurogenesis. The results demonstrate that neural progenitors display particular vulnerability, leading to downstream differentiation decreases in neurons or astrocytes. Progenitors display indicators of quiescence suggested by changes in proliferation, differentiation, epigenetic and metabolic markers. While restoring methionine levels rescued neuron production, there were continued differences in energy metabolism and methylation marks, presumably leading to compromised or delayed gliogenesis. These findings prompt further questions about how metabolic substrates coordinate developmental timing and impact cell fate decisions.In addition to nutrient availability, a recent preprint by Rodriguez Salazar and colleagues evaluates how mitochondrial dynamics influence astrocyte morphology and maturation in mice and rats (Salazar et al., 2024 preprint). During postnatal development, astrocytes undergo structural and functional changes to progress to a mature state, shifting from anabolic growth to catabolic support of increased energy demands (Zehnder et al., 2021; Marina et al., 2018). The balance of mitochondria fission, fusion and transport is essential for coordinating energy metabolism and specialized functions of astrocytes (Tábara et al., 2024). The authors discovered that Drp-1-mediated mitochondrial fission enables the localization of mitochondria to distal astrocyte processes to support higher degrees of branching and more-complex morphologies. The resulting high distal mitochondrial content is required to establish proper Cx43 gap junction protein abundance and an evenly dispersed astrocyte domain organization across the cortex. Their results indicate the importance of mitochondria dynamics to support structural changes in maturing astrocytes, which mediate complex intercellular, synaptic and metabolic regulation. Notably, mitochondria fission drives high glycolytic activity due to decreased oxidative phosphorylation efficiency and high ROS production (Zong et al., 2024; Chen and Chan, 2017). Mature astrocytes have high glycolysis influx and lactate production that provides metabolic fuel for surrounding neurons. The relationship between mitochondria fission, glycolytic activity and morphological complexity during astrocyte maturation supports cortical development.Collectively, these studies h","journal":"Development","year":2025,"id":560460,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9572,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":228389,"name":"Madeline G. Andrews","orcid":"0000-0002-5154-5081","position":1,"is_corresponding":false},{"id":1462402,"name":"Taylor R. Pennington","orcid":"0009-0006-3694-5489","position":0,"is_corresponding":true}],"reference_count":24,"raw_metadata":null,"created_at":"2026-07-19T02:55:42.883572Z","pmid":"39817598","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}