From Alex Eve (executive director of the society journal Development) and James Briscoe (editor-in-chief of Development):
"We contend that Development is a key example that demonstrates the lack of correlation between the impact factor metric, and the trust, reputation and scientific rigour of the articles we publish."
"The elephant in the room: impact factor"
Alex Eve and James Briscoe, 2026 editorial
https://journals.biologists.com/dev/article/153/12/dev205838/371997/The-elephant-in-the-room-impact-factor
New preprint: "Stoichiometric transcription factor partnerships control GABAergic neuron fate allocation."
Cell identity in development is often described as a combinatorial transcription factor "code." We find it is also quantitative: not only which factors are present, but their relative abundance, can shape a cell's fate.
In the developing basal ganglia, a pool of undifferentiated progenitors gives rise to several GABAergic neuron types, including D1 and D2 medium spiny neurons. Using our in vivo clonal perturbation sequencing and clone2vec, we find that losing SP9 shifts the clonal fate bias of progenitors from D2 neurons toward other GABAergic fates.
The readout uses two modes of genome binding: at GC-rich promoters SP9 binds DNA directly and activates; at distal enhancers it binds indirectly, tethered by DLX, acting as a combinatorial repressor with the NuRD complex. When DLX is in excess it sequesters SP9 away from its activating targets, so a graded shift in the SP9:DLX ratio becomes a discrete fate choice. An SP9 variant linked to neurodevelopmental disorders impairs the activator mode.
With thanks to the team, collaborators, and to #SFARI, the #DFG and the #NLMFF.
Combinatorial transcription factor (TF) codes specify neuronal fates, yet how quantitative differences in interacting TFs shape these decisions remains unresolved. We address this in the developing basal ganglia, where a pool of undifferentiated progenitors gives rise to both D1 and D2 medium spiny neurons (MSNs). Combining sparse in vivo CRISPR perturbation, lineage barcoding, and single-cell transcriptomics in mice, we find that loss of Sp9 shifts clonal fate bias from D2 toward D1 MSNs and intercalated cells. Mechanistically, chromatin profiling and biochemical assays show that at GC-rich promoters, SP9 binds DNA directly and activates transcription. At distal enhancers, SP9 binds indirectly, tethered by DLX factors, represses activity, and associates with the NuRD corepressor complex. The relative abundance of SP9 and DLX selects between these modes. These findings extend the combinatorial TF code beyond factor identity to relative proportions, with relevance to neurodevelopmental disorders. ### Competing Interest Statement The authors have declared no competing interest. Deutsche Forschungsgemeinschaft, https://ror.org/018mejw64, 549328218 Simons Foundation, https://ror.org/01cmst727, SFI-AN-AR-Pilot-00009814 Nancy Lurie Marks Family Foundation European Molecular Biology Organization, https://ror.org/04wfr2810, EMBO Young Investigator Programme
New preprint from the lab!
How do brain progenitors choose between D1 and D2 medium spiny neurons? We find the *relative levels* of SP9 and DLX TFs tip the balance: SP9 activates D2 genes at promoters, and represses D1 enhancers via DLX/NuRD.
Proud of the team — combining sparse in vivo CRISPR, lineage barcoding, scRNA-seq, ChIP-seq, CUT&RUN and proteomics for mechanistic depth in in vivo functional genomics.
BMS Seminar:
Kristian Franze (PDN, Cambridge & MPZPM, Erlangen)
The chemo-mechanical regulation of brain development
TODAY! 1315 in MTC LT Gibbet Hill
Pierced ears and ear rings: Epithelial fusion and fracture in the developing zebrafish inner ear
Professor Tanya Whitfield
School of Biosciences, University of Sheffield
Wednesday 22 April 2026
1.15pm-2.15pm
IBRB Lecture Theatre, Gibbet Hill Campus
NEW Paper from the Saunders lab
Identification of optimal fluorophores for use in the Drosophila embryo
Chapa-y-Lazo et al.
https://www.molbiolcell.org/doi/full/10.1091/mbc.E25-12-0600
The ABC of my fave things in this paper:
* ABOLISHING both silencing AND leakiness of SynNotch (check out the DTA-based demo of this 😍) while preserving high efficiency, in pluripotent & differentiating cells
* BOOSTING signal during #PUFFFIN neighbour-labelling
* CITING Robbie Burns (1786) 🏴
https://www.biorxiv.org/content/10.64898/2026.03.22.713470v1
The establishment of genetic circuits in pluripotent stem cells (PSCs) allows to model and manipulate developmental events. However, prototyping complex circuitry remains challenging, due to limitations in screening circuit components and transgene silencing. Here, we introduce KELPE: PSCs with two silencing-resistant insulated genomic landing pads targeted to genomic safe harbour sites. KELPE cells enable the stable integration of multiple transgenes into the same genomic region, facilitating fair comparisons of genetic circuit components. We demonstrate this by fine-tuning "synthetic neighbour-labelling" technologies. We first generate optimised PUFFFIN PSCs, which report on cell-cell interactions by fluorescently labelling wild-type neighbours. We then generate new synNotch "receiver" PSCs, which can trigger expression of any transgene following interaction with a synthetic ligand presented by "sender" cells of interest. We describe an optimised circuit syntax that abolishes ligand-independent transgene induction in receiver PSCs, and showcase this by synthetically programming cell death in receiver cells engineered to express a toxin following interaction with sender cells. In summary, we describe a new cell line that facilitates silencing-resistant transgene expression and prototyping of synthetic biology tools in a developmentally-relevant model. ### Competing Interest Statement The authors have declared no competing interest.
Xenbase
Albert Cardona
Christian Mayer
mechanochemistry
Sally Lowell